Improved learning and memory in aged rats with chronic administration of the nicotinic receptor agonist GTS-21

Brain Res. 1995 Mar 20;674(2):252-9. doi: 10.1016/0006-8993(94)01449-r.


The ability of two synthetic nicotine receptor ligands, TGS-21 and DMAB, to chronically enhance the cognitive function of aged rats was evaluated in three diverse tasks and compared to the cognition-enhancing effects of nicotine administration. 15 min prior to daily behavioral testing, aged 22-24 month old rats received an i.p. injection of nicotine (.02 mg/kg), GTS-21 (1 mg/kg), DMAB (2mg/kg), or saline vehicle and were tested in either one-way active avoidance pole jumping, Lashley III maze, or a 17-arm radial maze. GTS-21 pretreatment was as effective as nicotine for enhancing the acquisition of aged rats in both one-way active avoidance and Lashley III maze training. In 17-arm radial maze testing, GTS-21 improved both general learning and reference (long-term) memory to the same extent as nicotine. Although DMAB pretreatment enhanced reference memory in 17-arm radial maze testing to the same as nicotine, it did not affect general learning in this complex task and did not exert any cognition-enhancing effects in Lashley III maze training. These results indicate that GTS-21 has cognition-enhancing abilities in aged rats that are comparable to those of nicotine in a variety of behavioral tasks. Since GTS-21 acts preferentially on brain nicotinic receptors and is less toxic than nicotine, thses results further indicate that GTS-21 may have substantive therapeutic value in the treatment of age-associated memory impairment (AAMI) and/or Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / psychology*
  • Anabasine / analogs & derivatives
  • Anabasine / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Benzylidene Compounds / pharmacology*
  • Cognition / drug effects
  • Learning / drug effects*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory, Short-Term / drug effects
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology*
  • Psychotropic Drugs / pharmacology
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Stimulation, Chemical


  • 3-(4-dimethylaminobenzylidene)anabaseine
  • Benzylidene Compounds
  • Nicotinic Agonists
  • Psychotropic Drugs
  • Pyridines
  • Nicotine
  • 3-(2,4-dimethoxybenzylidene)anabaseine
  • Anabasine